AGER and Hyperglycemia: Chaldakov et al. (2007) reported that the plasma BDNF levels of patients with T2DM were lower than those of healthy controls, and hyperglycemia could inhibit the output of BDNF from the brain. Ward et al. (2019) showed that diabetes could damage the integrity of the Neurovascular unit (NVU) in the hippocampus and reduce BDNF levels in endothelial cells and HT22 hippocampal neurons. Diabetes-induced reduction in BDNF secretion, along with increased receptor for advanced glycation end products (RAGE), contributes to cerebrovascular dysfunction and cognitive decline (Kim and Song, 2020).